Mixter P F, Russell J Q, Budd R C
Department of Medicine, University of Vermont College of Medicine, Burlington 05405-0068.
J Autoimmun. 1994 Dec;7(6):697-710. doi: 10.1006/jaut.1994.1055.
The Fas/APO-1 (Fas) antigen is a cell surface protein that mediates apoptosis and belongs to the tumor necrosis factor receptor family. The lymphoproliferative (lpr) anomaly in mice results from a retroviral disruption within the fas gene. Mice that are homozygous for the lpr mutation accumulate large numbers of T lymphocytes and exhibit an autoimmune syndrome resembling systemic lupus erythematosus. A possible explanation for this process is that in the absence of Fas antigen, lpr T cells may be resistant to normal peripheral deletional signals. The bacterial superantigen staphylococcal enterotoxin B (SEB) rapidly induces anergy and deletion by apoptosis of reactive T lymphocytes in normal mice. Administration of SEB to adult lpr mice results in the delayed induction of both unresponsiveness and deletion of V beta 8+ lymph node cells. This is not due merely to an increased thymic output in lpr mice; the delayed induction of tolerance and elimination of reactive lpr T cells by superantigens are intrinsic properties of the cells. The progressive lymphadenopathy in lpr mice may reflect a process of lymphoaccumulation rather than lymphoproliferation. A delay in tolerance induction and elimination of self-reactive T cells could have profound influence on the autoimmune diathesis of lpr mice.
Fas/APO-1（Fas）抗原是一种介导细胞凋亡的细胞表面蛋白，属于肿瘤坏死因子受体家族。小鼠中的淋巴细胞增生（lpr）异常是由fas基因内的逆转录病毒破坏引起的。lpr突变纯合子小鼠会积累大量T淋巴细胞，并表现出类似于系统性红斑狼疮的自身免疫综合征。对此过程的一种可能解释是，在缺乏Fas抗原的情况下，lpr T细胞可能对正常的外周缺失信号具有抗性。细菌超抗原葡萄球菌肠毒素B（SEB）可迅速诱导正常小鼠中反应性T淋巴细胞发生无反应性并通过凋亡使其缺失。给成年lpr小鼠注射SEB会导致Vβ8 +淋巴结细胞无反应性和缺失的诱导延迟。这不仅仅是由于lpr小鼠胸腺输出增加所致；超抗原对lpr T细胞耐受性的延迟诱导和反应性lpr T细胞的消除是细胞的固有特性。lpr小鼠中进行性淋巴结病可能反映的是淋巴细胞积聚过程而非淋巴细胞增殖。耐受性诱导和自身反应性T细胞消除的延迟可能对lpr小鼠的自身免疫素质产生深远影响。
